Diabetes breakthrough: Fish oil shown to reverse insulin resistance
The study, funded by FAPESP, was conducted on rats exhibiting a condition similar to type 2 diabetes, characterized by high blood sugar levels due to diminished insulin effectiveness. While the rats were not obese, the research focused on the effects of omega-3 fatty acids, such as those found in fish oil, on insulin resistance in non-obese subjects—a condition not well understood.
The researchers observed that administering 2 grams of fish oil per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA) three times per week for eight weeks reduced insulin resistance in these non-obese rats. Additionally, the rats showed improved blood sugar levels, reduced inflammatory markers, and improvements in lipid features, including total cholesterol, LDL (bad cholesterol), and triglycerides.
These results, from preclinical trials, offer hope for non-obese individuals with type 2 diabetes, who make up approximately 10-20% of the global total of people with the condition.
'Our experiments involved Goto-Kakizaki (GK) rats, an animal model for non-obese type 2 diabetes,' explained Rui Curi, Director of the Butantan Institute's Education Center, Professor at Cruzeiro do Sul University (UNICSUL), and the study coordinator. 'We found that insulin resistance can be reduced in these animals by modulating the inflammatory response, which shifts the profile of defense cells (lymphocytes) from a pro-inflammatory state to an anti-inflammatory state. This process is similar to the effect omega-3 fatty acid supplementation has on obese individuals with insulin resistance.'
Alterations in lymphocytes, white blood cells involved in the immune response, influence other immune system cells, triggering a cascade effect. 'Previous studies showed changes in lymphocytes and macrophages in non-obese rats with insulin resistance,' Curi said. 'In these cases, the cells produce more pro-inflammatory cytokines, a pattern also found in obese individuals with diabetes.'
The study aimed to determine whether fish oil supplementation could reverse these specific alterations in lymphocytes, which had been observed in earlier research. The findings confirm that inflammation is a key factor in insulin resistance, even in the absence of obesity.
Renata Gorjão, the last author of the study and Co-Director of UNICSUL's Program of Graduate Studies in Health Sciences, added, 'Our findings provide valuable insights into the link between inflammation and insulin resistance in non-obese animals, confirming that inflammation is a crucial factor in diabetes even without obesity.'
The research is part of a larger project supported by FAPESP, focusing on insulin resistance in non-obese animals. While obesity is a significant risk factor for diabetes, the study also highlights that genetic factors and systemic inflammation can contribute to insulin resistance in non-obese individuals.
'Most obese people experience chronic low-level inflammation, which affects insulin signaling pathways. In the non-obese model, this characteristic of adipose tissue is absent, but systemic inflammation is still present,' Curi explained.
In a previous study, the group demonstrated systemic inflammation in non-obese GK rats with insulin resistance. Further research found early breakdowns in anti-inflammatory mechanisms in non-obese GK rats, including reductions in regulatory T-cells (Tregs) in lymph nodes.
The fish oil supplementation reversed this pro-inflammatory profile, showing significant anti-inflammatory effects and improving the balance of Th1 and Th17 cells (lymphocyte subtypes critical to inflammation). This led to an increase in Tregs, which inhibit pro-inflammatory lymphocytes, ultimately reducing insulin resistance in the rats.
Despite promising results, the researchers stress the need for further studies, especially in human trials, to confirm these findings and determine the ideal dose and type of omega-3 fatty acids.
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